ABSTRACT The electrochemical and chemical reduction of the antitumoral drugs doxorubicin andepirubicin is investigated in aprotic and protic media, in the presence and absence of oxygen bycoupled electrochemical and spectral techniques. The cyclic voltammetry with stationary androtating disc electrode (RDE) points out a quite similar electrochemical behaviour, consisting oftwo electron transfers and evidence as intermediate species the anion-radical (A–.), the dianion(A2–) and the protonated species AH-, AH., AH2. EPR and optical spectra registered during theelectrochemical reduction allow the identification of these species and suggest the possibility ofback oxidation of the drug by electron transfer to molecular oxygen. AM1 semiempirical MOcalculationsallow a rationalisation of the experimental results regarding the reactivity in redoxprocesses and outline the dominant role of the anthraquinone moiety. Biological implications ofthe reductive activation of molecular oxygen are also discussed.